#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly


Cellular and viral life cycles are connected through multiple, though poorly understood, mechanisms. Parvoviruses infect humans and a broad spectrum of animals, causing a variety of diseases, but they are also used in experimental cancer therapy and serve as vectors for gene therapy. Parvoviruses can only multiply in proliferating cells providing essential replicative and transcriptional functions. However, it is unknown whether the cell cycle regulatory machinery may also control parvovirus assembly. We found that the nuclear translocation of parvovirus MVM capsid subunits (VPs) was highly dependent on physiological cell cycle regulations in mammalian fibroblasts, including: quiescence, progression through G1/S boundary, DNA synthesis, and cell to cell contacts. VPs nuclear translocation was significantly more sensitive to cell cycle controls than viral genome replication and gene expression. The results support nuclear capsid assembly as the major driving process of parvoviruses biological hallmarks, such as pathogenesis in proliferative tissues and tropism for cancer cells. In addition, disturbing the tight coupling of parvovirus assembly with the cell cycle may determine viral persistence in quiescent and post-mitotic host tissues. These findings may contribute to understand cellular regulations on the assembly of other nuclear eukaryotic viruses, and to develop cell cycle-based avenues for antiviral therapy.


Vyšlo v časopise: The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004920
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004920

Souhrn

Cellular and viral life cycles are connected through multiple, though poorly understood, mechanisms. Parvoviruses infect humans and a broad spectrum of animals, causing a variety of diseases, but they are also used in experimental cancer therapy and serve as vectors for gene therapy. Parvoviruses can only multiply in proliferating cells providing essential replicative and transcriptional functions. However, it is unknown whether the cell cycle regulatory machinery may also control parvovirus assembly. We found that the nuclear translocation of parvovirus MVM capsid subunits (VPs) was highly dependent on physiological cell cycle regulations in mammalian fibroblasts, including: quiescence, progression through G1/S boundary, DNA synthesis, and cell to cell contacts. VPs nuclear translocation was significantly more sensitive to cell cycle controls than viral genome replication and gene expression. The results support nuclear capsid assembly as the major driving process of parvoviruses biological hallmarks, such as pathogenesis in proliferative tissues and tropism for cancer cells. In addition, disturbing the tight coupling of parvovirus assembly with the cell cycle may determine viral persistence in quiescent and post-mitotic host tissues. These findings may contribute to understand cellular regulations on the assembly of other nuclear eukaryotic viruses, and to develop cell cycle-based avenues for antiviral therapy.


Zdroje

1. Stumpf CR, Moreno MV, Olshen AB, Taylor BS, Ruggero D (2013) The translational landscape of the mammalian cell cycle. Mol Cell 52: 574–582. doi: 10.1016/j.molcel.2013.09.018 24120665

2. Cho RJ, Huang M, Campbell MJ, Dong H, Steinmetz L, et al. (2001) Transcriptional regulation and function during the human cell cycle. Nat Genet 27: 48–54. 11137997

3. Mukherji M, Bell R, Supekova L, Wang Y, Orth AP, et al. (2006) Genome-wide functional analysis of human cell-cycle regulators. Proc Natl Acad Sci U S A 103: 14819–14824. 17001007

4. Weis K (2003) Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle. Cell 112: 441–451. 12600309

5. Makhnevych T, Lusk CP, Anderson AM, Aitchison JD, Wozniak RW (2003) Cell cycle regulated transport controlled by alterations in the nuclear pore complex. Cell 115: 813–823. 14697200

6. Gorlich D, Prehn S, Laskey RA, Hartmann E (1994) Isolation of a protein that is essential for the first step of nuclear protein import. Cell 79: 767–778. 8001116

7. Stade K, Ford CS, Guthrie C, Weis K (1997) Exportin 1 (Crm1p) is an essential nuclear export factor. Cell 90: 1041–1050. 9323132

8. Imperiale MJ, Major EO (2007) Polyomaviruses. In: Knipe DM, Howley PM, editors. Fields Virology. Fifth Edition ed. Philadelphia, PA: Lippincott Williams & Wilkins. pp. 2263–2298.

9. Hebner CM, Laimins LA (2006) Human papillomaviruses: basic mechanisms of pathogenesis and oncogenicity. Rev Med Virol 16: 83–97. 16287204

10. Flemington EK (2001) Herpesvirus lytic replication and the cell cycle: arresting new developments. J Virol 75: 4475–4481. 11312317

11. Paladino P, Marcon E, Greenblatt J, Frappier L (2014) Identification of herpesvirus proteins that contribute to G1/S arrest. J Virol 88: 4480–4492. doi: 10.1128/JVI.00059-14 24501404

12. Chaurushiya MS, Weitzman MD (2009) Viral manipulation of DNA repair and cell cycle checkpoints. DNA Repair (Amst) 8: 1166–1176. doi: 10.1016/j.dnarep.2009.04.016 19473887

13. Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461: 1071–1078. doi: 10.1038/nature08467 19847258

14. Davy C, Doorbar J (2007) G2/M cell cycle arrest in the life cycle of viruses. Virology 368: 219–226. 17675127

15. Laguette N, Bregnard C, Hue P, Basbous J, Yatim A, et al. (2014) Premature activation of the SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing. Cell 156: 134–145. doi: 10.1016/j.cell.2013.12.011 24412650

16. Tijssen P, Agbandje-McKenna M, Almendral JM, Bergoin M, Flegel TW, et al. (2011) Family Parvoviridae. In: King AMQ, Adams JM, Carsterns EB, Lefkowitz EJ, editors. ICTV Report 2011. Oxford, U.K.: Elsevier. pp. 405–425.

17. Cotmore SF, Agbandje-McKenna M, Chiorini JA, Mukha DV, Pintel DJ, et al. (2013) The family Parvoviridae. Arch Virol 159: 1239–1247. doi: 10.1007/s00705-013-1914-1 24212889

18. Berns N, Parrish CR (2007) Parvoviridae. Parvoviridae. 5th ed. Philadelphia, PA: Lippincott Willians and Wilkins.

19. Weitzman MD (2006) The parvovirus life cycle: an introduction to molecular interactions important for infection. In: Kerr JR, Cotmore SF, Bloom ME, Linden RM, Parrish CR, editors. Parvoviruses. London, U.K.: Hodder Arnold. pp. 143–156.

20. Cotmore SF, Tattersall P (1987) The autonomously replicating parvoviruses of vertebrates. Adv Virus Res 33: 91–174. 3296697

21. Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129: 665–679. 17512402

22. Bashir T, Horlein R, Rommelaere J, Willwand K (2000) Cyclin A activates the DNA polymerase delta-dependent elongation machinery in vitro: A parvovirus DNA replication model. Proc Natl Acad Sci U S A 97: 5522–5527. 10792046

23. Deleu L, Fuks F, Spitkovsky D, Horlein R, Faisst S, et al. (1998) Opposite transcriptional effects of cyclic AMP-responsive elements in confluent or p27KIP-overexpressing cells versus serum-starved or growing cells. Mol Cell Biol 18: 409–419. 9418888

24. Deleu L, Pujol A, Faisst S, Rommelaere J (1999) Activation of promoter P4 of the autonomous parvovirus minute virus of mice at early S phase is required for productive infection. J Virol 73: 3877–3885. 10196282

25. Raj K, Ogston P, Beard P (2001) Virus-mediated killing of cells that lack p53 activity. Nature 412: 914–917. 11528480

26. Luo Y, Kleiboeker S, Deng X, Qiu J (2013) Human parvovirus B19 infection causes cell cycle arrest of human erythroid progenitors at late S phase that favors viral DNA replication. J Virol 87: 12766–12775. doi: 10.1128/JVI.02333-13 24049177

27. Adeyemi RO, Landry S, Davis ME, Weitzman MD, Pintel DJ (2010) Parvovirus minute virus of mice induces a DNA damage response that facilitates viral replication. PLoS Pathog 6: e1001141. doi: 10.1371/journal.ppat.1001141 20949077

28. Adeyemi RO, Fuller MS, Pintel DJ (2014) Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA. PLoS Pathog 10: e1004055. doi: 10.1371/journal.ppat.1004055 24699724

29. Cotmore SF, Tattersall P (1992) In vivo resolution of circular plasmids containing concatemer junction fragments from minute virus of mice DNA and their subsequent replication as linear molecules. J Virol 66: 420–431. 1530771

30. Berthet C, Raj K, Saudan P, Beard P (2005) How adeno-associated virus Rep78 protein arrests cells completely in S phase. Proc Natl Acad Sci U S A 102: 13634–13639. 16157891

31. Geletneky K, Huesing J, Rommelaere J, Schlehofer JR, Leuchs B, et al. (2012) Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol. BMC Cancer 12: 99. doi: 10.1186/1471-2407-12-99 22436661

32. Dismuke DJ, Tenenbaum L, Samulski RJ (2013) Biosafety of recombinant adeno-associated virus vectors. Curr Gene Ther 13: 434–452. 24195602

33. Siegel G (1988) Patterns of parvovirus disease in animals. In: Pattison JR, editor. Parvoviruses and Human Disease. Boca Raton, FL: CRC Press.

34. Maga G, Hubscher U (2003) Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci 116: 3051–3060. 12829735

35. Almendral JM, Sommer D, Macdonald-Bravo H, Burckhardt J, Perera J, et al. (1988) Complexity of the early genetic response to growth factors in mouse fibroblasts. Mol Cell Biol 8: 2140–2148. 2898731

36. Lombardo E, Ramirez JC, Agbandje-McKenna M, Almendral JM (2000) A beta-stranded motif drives capsid protein oligomers of the parvovirus minute virus of mice into the nucleus for viral assembly. J Virol 74: 3804–3814. 10729155

37. Riolobos L, Reguera J, Mateu MG, Almendral JM (2006) Nuclear transport of trimeric assembly intermediates exerts a morphogenetic control on the icosahedral parvovirus capsid. J Mol Biol 357: 1026–1038. 16469332

38. Riolobos L, Valle N, Hernando E, Maroto B, Kann M, et al. (2010) Viral oncolysis that targets Raf-1 signaling control of nuclear transport. J Virol 84: 2090–2099. doi: 10.1128/JVI.01550-09 19939915

39. Lopez-Bueno A, Mateu MG, Almendral JM (2003) High mutant frequency in populations of a DNA virus allows evasion from antibody therapy in an immunodeficient host. J Virol 77: 2701–2708. 12552010

40. Kaufmann B, Lopez-Bueno A, Mateu MG, Chipman PR, Nelson CD, et al. (2007) Minute virus of mice, a parvovirus, in complex with the Fab fragment of a neutralizing monoclonal antibody. J Virol 81: 9851–9858. 17626084

41. Bravo R, Macdonald-Bravo H (1985) Changes in the nuclear distribution of cyclin (PCNA) but not its synthesis depend on DNA replication. EMBO J 4: 655–661. 2861088

42. Lombardo E, Ramirez JC, Garcia J, Almendral JM (2002) Complementary roles of multiple nuclear targeting signals in the capsid proteins of the parvovirus minute virus of mice during assembly and onset of infection. J Virol 76: 7049–7059. 12072505

43. Maroto B, Ramirez JC, Almendral JM (2000) Phosphorylation status of the parvovirus minute virus of mice particle: mapping and biological relevance of the major phosphorylation sites. J Virol 74: 10892–10902. 11069983

44. O'Reilly AJ, Dacks JB, Field MC (2011) Evolution of the karyopherin-beta family of nucleocytoplasmic transport factors; ancient origins and continued specialization. PLoS One 6: e19308. doi: 10.1371/journal.pone.0019308 21556326

45. Enenkel C, Blobel G, Rexach M (1995) Identification of a yeast karyopherin heterodimer that targets import substrate to mammalian nuclear pore complexes. J Biol Chem 270: 16499–16502. 7622450

46. Kalderon D, Roberts BL, Richardson WD, Smith AE (1984) A short amino acid sequence able to specify nuclear location. Cell 39: 499–509. 6096007

47. Robbins J, Dilworth SM, Laskey RA, Dingwall C (1991) Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence. Cell 64: 615–623. 1991323

48. Pollard VW, Michael WM, Nakielny S, Siomi MC, Wang F, et al. (1996) A novel receptor-mediated nuclear protein import pathway. Cell 86: 985–994. 8808633

49. Lee BJ, Cansizoglu AE, Suel KE, Louis TH, Zhang Z, et al. (2006) Rules for nuclear localization sequence recognition by karyopherin beta 2. Cell 126: 543–558. 16901787

50. Iyer VR, Eisen MB, Ross DT, Schuler G, Moore T, et al. (1999) The transcriptional program in the response of human fibroblasts to serum. Science 283: 83–87. 9872747

51. Cotmore SF, D'Abramo AM Jr., Carbonell LF, Bratton J, Tattersall P (1997) The NS2 polypeptide of parvovirus MVM is required for capsid assembly in murine cells. Virology 231: 267–280. 9168889

52. Bouayad D, Pederzoli-Ribeil M, Mocek J, Candalh C, Arlet JB, et al. (2012) Nuclear-to-cytoplasmic relocalization of the proliferating cell nuclear antigen (PCNA) during differentiation involves a chromosome region maintenance 1 (CRM1)-dependent export and is a prerequisite for PCNA antiapoptotic activity in mature neutrophils. J Biol Chem 287: 33812–33825. 22846997

53. Kim BJ, Lee H (2008) Lys-110 is essential for targeting PCNA to replication and repair foci, and the K110A mutant activates apoptosis. Biol Cell 100: 675–686. doi: 10.1042/BC20070158 18498247

54. Churchill JR, Studzinski GP (1970) Thymidine as synchronizing agent. 3. Persistence of cell cycle patterns of phosphatase activities and elevation of nuclease activity during inhibition of DNA synthesis. J Cell Physiol 75: 297–303. 5449696

55. Zadori Z, Szelei J, Lacoste MC, Li Y, Gariepy S, et al. (2001) A viral phospholipase A2 is required for parvovirus infectivity. Dev Cell 1: 291–302. 11702787

56. Porwal M, Cohen S, Snoussi K, Popa-Wagner R, Anderson F, et al. (2013) Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis. PLoS Pathog 9: e1003671. doi: 10.1371/journal.ppat.1003671 24204256

57. Tattersall P (1972) Replication of the parvovirus MVM. I. Dependence of virus multiplication and plaque formation on cell growth. J Virol 10: 586–590. 4673484

58. Rhode SL 3rd (1973) Replication process of the parvovirus H-1. I. Kinetics in a parasynchronous cell system. J Virol 11: 856–861. 4736535

59. Siegl G, Gautschi M (1973) The multiplication of parvovirus Lu3 in a synchronized culture system. II. Biochemical characteristics of virus replication. Arch Gesamte Virusforsch 40: 119–127. 4266337

60. Mattaj IW, Englmeier L (1998) Nucleocytoplasmic transport: the soluble phase. Annu Rev Biochem 67: 265–306. 9759490

61. Qi M, Elion EA (2005) MAP kinase pathways. J Cell Sci 118: 3569–3572. 16105880

62. Aoki K, Kumagai Y, Sakurai A, Komatsu N, Fujita Y, et al. (2013) Stochastic ERK activation induced by noise and cell-to-cell propagation regulates cell density-dependent proliferation. Mol Cell 52: 529–540. doi: 10.1016/j.molcel.2013.09.015 24140422

63. Wang S, Ghosh RN, Chellappan SP (1998) Raf-1 physically interacts with Rb and regulates its function: a link between mitogenic signaling and cell cycle regulation. Mol Cell Biol 18: 7487–7498. 9819434

64. Dasgupta P, Sun J, Wang S, Fusaro G, Betts V, et al. (2004) Disruption of the Rb—Raf-1 interaction inhibits tumor growth and angiogenesis. Mol Cell Biol 24: 9527–9541. 15485920

65. Gardiner EM, Tattersall P (1988) Mapping of the fibrotropic and lymphotropic host range determinants of the parvovirus minute virus of mice. J Virol 62: 2605–2613. 3392768

66. Tattersall P, Bratton J (1983) Reciprocal productive and restrictive virus-cell interactions of immunosuppressive and prototype strains of minute virus of mice. J Virol 46: 944–955. 6602222

67. Baserga R (1978) Resting cells and the G1 phase of the cell cycle. J Cell Physiol 95: 377–382. 649675

68. Tobey RA (1973) Production and characterization of mammalian cells reversibly arrested in G1 by growth in isoleucine-deficient medium. Methods Cell Biol 6: 67–112. 4585084

69. Huberman JA (1981) New views of the biochemistry of eucaryotic DNA replication revealed by aphidicolin, an unusual inhibitor of DNA polymerase alpha. Cell 23: 647–648. 6784928

70. Bootsma D, Budke L, Vos O (1964) Studies on Synchronous Division of Tissue Culture Cells Initiated by Excess Thymidine. Exp Cell Res 33: 301–309. 14109144

71. Rubio MP, Lopez-Bueno A, Almendral JM (2005) Virulent variants emerging in mice infected with the apathogenic prototype strain of the parvovirus minute virus of mice exhibit a capsid with low avidity for a primary receptor. J Virol 79: 11280–11290. 16103180

72. Sanchez-Martinez C, Grueso E, Carroll M, Rommelaere J, Almendral JM (2012) Essential role of the unordered VP2 n-terminal domain of the parvovirus MVM capsid in nuclear assembly and endosomal enlargement of the virion fivefold channel for cell entry. Virology 432: 45–56. doi: 10.1016/j.virol.2012.05.025 22727830

73. Crawford LV (1966) A minute virus of mice. Virology 29: 605–612. 5945715

74. Bonnard GD, Manders EK, Campbell DA Jr., Herberman RB, Collins MJ Jr. (1976) Immunosuppressive activity of a subline of the mouse EL-4 lymphoma. Evidence for minute virus of mice causing the inhibition. J Exp Med 143: 187–205. 1244418

75. Merchlinsky MJ, Tattersall PJ, Leary JJ, Cotmore SF, Gardiner EM, et al. (1983) Construction of an infectious molecular clone of the autonomous parvovirus minute virus of mice. J Virol 47: 227–232. 6345805

76. Boissy R, Astell CR (1985) An Escherichia coli recBCsbcBrecF host permits the deletion-resistant propagation of plasmid clones containing the 5'-terminal palindrome of minute virus of mice. Gene 35: 179–185. 3896934

77. Ramirez JC, Santaren JF, Almendral JM (1995) Transcriptional inhibition of the parvovirus minute virus of mice by constitutive expression of an antisense RNA targeted against the NS-1 transactivator protein. Virology 206: 57–68. 7831812

78. Clemens DL, Wolfinbarger JB, Mori S, Berry BD, Hayes SF, et al. (1992) Expression of Aleutian mink disease parvovirus capsid proteins by a recombinant vaccinia virus: self-assembly of capsid proteins into particles. J Virol 66: 3077–3085. 1313919

79. Clemens KE, Cerutis DR, Burger LR, Yang CQ, Pintel DJ (1990) Cloning of minute virus of mice cDNAs and preliminary analysis of individual viral proteins expressed in murine cells. J Virol 64: 3967–3973. 2164605

80. Christensen J, Storgaard T, Bloch B, Alexandersen S, Aasted B (1993) Expression of Aleutian mink disease parvovirus proteins in a baculovirus vector system. J Virol 67: 229–238. 8380073

81. Hernando E, Llamas-Saiz AL, Foces-Foces C, McKenna R, Portman I, et al. (2000) Biochemical and physical characterization of parvovirus minute virus of mice virus-like particles. Virology 267: 299–309. 10662625

82. Kajigaya S, Fujii H, Field A, Anderson S, Rosenfeld S, et al. (1991) Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions. Proc Natl Acad Sci U S A 88: 4646–4650. 1711206

83. Tattersall P, Cawte PJ, Shatkin AJ, Ward DC (1976) Three structural polypeptides coded for by minite virus of mice, a parvovirus. J Virol 20: 273–289. 988192

84. Knowles WJ, Bologna ML (1983) Isolation of the chemical domains of human erythrocyte spectrin. Methods Enzymol 96: 305–313. 6656634

85. Rubio MP, Guerra S, Almendral JM (2001) Genome replication and postencapsidation functions mapping to the nonstructural gene restrict the host range of a murine parvovirus in human cells. J Virol 75: 11573–11582. 11689639

86. Almendral JM, Huebsch D, Blundell PA, Macdonald-Bravo H, Bravo R (1987) Cloning and sequence of the human nuclear protein cyclin: homology with DNA-binding proteins. Proc Natl Acad Sci U S A 84: 1575–1579. 2882507

87. Bravo R, Frank R, Blundell PA, Macdonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature 326: 515–517. 2882423

88. Williams NG, Paradis H, Agarwal S, Charest DL, Pelech SL, et al. (1993) Raf-1 and p21v-ras cooperate in the activation of mitogen-activated protein kinase. Proc Natl Acad Sci U S A 90: 5772–5776. 8390681

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2015 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#